In many cases naturally occurring animal models of human genetic disorders, especially those affecting the nervous system, have not been described. In those instances where the gene defect has been identified, the introduction of mutant DNA into the germ line of mice can provide a unique opportunity to generate mice having appropriate phenotypes where disease pathogenesis can be studied. Transgenic mice are generated by microinjection of DNA into fertilized eggs, by receptor complex targeting of DNA, and by retroviral gene transfer. Introduction of murine embryonic stem cells into blastocyst stage mouse embryos that have been genetically modified by gene targeting also permits the establishment of mouse strains carrying appropriate mutations. Murine models of Gaucher disease and other inherited disorders are being produced using these techniques. Such transgenic mouse models of human disorders will provide valuable tools for the evaluation of new treatments, including protein/enzyme replacement, cellular transplantation, and gene transfer therapies. Development and tissue specific expression of genes can also be investigated in these transgenic mice.